Brief Title
Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation
Official Title
Very Low-dose Total Body Irradiation in Combination With Total Lymphoid Irradiation and Anti-Thymocyte Globulin to Improve Donor Engraftment in Patients Undergoing Non-Myeloablative Hematopoietic Cell Transplantation
Brief Summary
The purpose of this study is to evaluate whether addition of a low dose of total body irradiation (TBI) to a standard preparation for transplant [total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG)] conditioning will help to augment donor chimerism without reducing tolerability of this regimen or increasing the risk of graft-vs-host disease (GVHD)
Detailed Description
Primary Objective: • Determine the proportion of patients with full donor T-cell chimerism at Day 28 following hematopoietic cell transplantation. Secondary Objectives: - Determine the risk of disease progression, overall and event free survival, and non-relapse mortality, following treatment with TLI; ATG; and TBI. - Determine the incidence of acute and chronic GVHD following treatment with TLI; ATG; and TBI. Exploratory Objectives: • Determine the changes in frequency of hematopoietic stem, progenitor, and mature cell subsets and the changes in cytokine milieu and cellular architecture in the bone marrow of patients receiving TLI compared to TLI+TBI.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning.
Secondary Outcome
Disease Progression
Condition
Acute Myeloid Leukemia
Intervention
Total body irradiation (TBI)
Study Arms / Comparison Groups
TBI+TLI
Description: TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Radiation
Estimated Enrollment
22
Start Date
November 5, 2018
Completion Date
November 17, 2020
Primary Completion Date
December 26, 2019
Eligibility Criteria
INCLUSION CRITERIA - Has a human leukocyte antigen (HLA)-matched or single allele mismatched adult sibling donor or unrelated donor. - Acute myeloid leukemia (AML); myelodysplastic syndrome (MDS); myeloproliferative disease syndrome (MPD)]; chronic lymphocytic leukemia (CLL); B- or T-cell non Hodgkin lymphoma (NHL); Hodgkin lymphoma (HL); or chronic myelomonocytic leukemia (CMML), suitable for treatment with allogeneic transplant after TLI and ATG reduced intensity conditioning. - Considered at high-risk for regimen-related toxicity from fully-ablative transplant conditioning (therefore reduced-intensity conditioning is recommended). - Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial. EXCLUSION CRITERIA - Uncontrolled bacterial, viral or fungal infection defined as currently taking medication and progression of clinical symptoms. - Progressive hemato lymphoid malignancy despite conventional therapy. - Chronic myelogenous leukemia (CML). - Active CNS involvement of the underlying malignancy. - HIV positive - Pregnant or lactating - Prior malignancy (EXCEPTION: diagnosed > 5 years ago without evidence of disease, OR treated ≤ 5 years ago but have a greater than 50% chance of life expectancy of ≥ 5 years for that malignancy). - Have a psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the primary physician would place the patient at an unacceptable risk from transplant. - Left ventricular ejection fraction (LEVF) < 30%, or uncontrolled cardiac failure - Diffusing capacity of lung for carbon monoxide (DLCO) < 40% predicted - Total bilirubin > 3 mg/dL - Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) > 4 x upper limit of normal (ULN) - Creatinine > 2 mg/dL and an estimated creatinine clearance < 40 mL/min - Poorly-controlled hypertension despite multiple antihypertensive medications - Karnofsky Performance Status (KPS) < 60%
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Robert Lowsky, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03734601
Organization ID
IRB-47407
Secondary IDs
BMT330
Responsible Party
Principal Investigator
Study Sponsor
Stanford University
Study Sponsor
Robert Lowsky, MD, Principal Investigator, Stanford University
Verification Date
May 2021